Abstract: Described embodiments provide systems and methods for performing cancer whole genome and transcriptome sequencing (cWGTS). A plurality of datasets can be generated based on sequencing of a tumor sample and a healthy control germline sample. A plurality of databases, comprising a first, second and third database, can be accessed. An RNA gene expression analysis can be performed to generate a first plurality of outputs. A DNA ploidy and allelic imbalance analysis can be performed to generate a second plurality of outputs. A variant calling analysis can be performed to generate a third plurality of outputs. A workflow may be implemented. Cohort classification scores and disease-specific classification scores for each individual level output in each of the first, second, and third pluralities of outputs can be generated. A report can be generated and provided to one or more users.